Genetic & Metabolic Bone Disorders Flashcards Preview

Specialty Medicine > Genetic & Metabolic Bone Disorders > Flashcards

Flashcards in Genetic & Metabolic Bone Disorders Deck (79):
1

What are the two general components of bone?

Organic and inorganic

2

What are the components of the organic component of bone?

Cells and matrix proteins

3

What are the cells that are in the organic part of bone? (4)

Osteoprogenitor cells
Osteoblasts
Osteocytes
Osteoclasts

4

What are the components of the matrix in organic bone?

Collagen type I
Non-collagenous proteins

5

What is the main component of inorganic bone?

calcium hydroxyapatite

6

What is unmineralized bone called?

Osteoid

7

What are osteoprogenitor cells?

Pluripotential mesenchymal cells that can form osteoblasts

8

What is the function of osteoblasts?

Synthesize and transport protein and osteoprotegerin, and initiate mineralization

9

What is the function of the RANK-L protein?

receptor on osteoblasts that binds to RANK receptor on osteoclasts to stimulate osteoclastic bone resorption

10

What is the precursor cell to osteoclasts?

Hematopoietic progenitor cells (fused monocytes/ Macrophages)

11

What is the role of osteoprotegerin?

Decoy receptor for RANKL, to prevent osteoclast activation

12

What are osteocytes? What is their function?

-Osteoblasts that have become surrounded by matrix
-Regulate daily serum Ca levels

13

How do osteoclasts appear histologically?

Multiple nuclei

14

Where is osteoprotegerin found?

Osteoclasts

15

How do osteocytes communicate with one another?

canaliculi

16

What is osteoid?

Unmineralized organic matrix that is lined by osteoblasts

17

What are the lacunae in which osteoclasts reside?

Howship lacunae

18

What part of the bone do osteoclasts not resorb?

Bone lined by osteoid or unmineralized cartilage

19

What is woven bone and laminar bone?

Woven bone = Collagen deposited in a random arrangement

Lamellar bone = bone deposited in an orderly, parallel arrangement

20

Where is woven bone usually present?

Fetal skeleton, at the growth plates, and in processes where there is very rapid bone production

21

True or false: Woven bone is almost always pathologic in adults

True

22

Where is lamellar bone located?

Only type of bone in adults

23

What are the 4 types of lamellar bone?

-Concentric
-Interstitial
-Inner circumferential
-Outer circumferential

24

Which is more sturdy--lamellar bone or woven bone?

Lamellar bone

25

What type of bone comprises calluses?

Woven bone

26

What are the causes of woven bone deposition in adults?

-calluses
-Fibrous dysplasia
-Areas surrounding tumors or infection

27

Which has more osteocytes: woven or lamellar bone?

Lamellar bone

28

What is an osteon?

Haversian canal + surrounding circular lamellar bone

29

What lines woven bone?

Osteoblasts

30

What are type I - IV of collagen?

I = bone
II = cartilage
III = reticular
IV = BM

31

What, generally, is achondroplasia?

Fusion of the epiphyseal plates before full maturity

32

What is the genetic cause of achondroplasia?

Reduction in the proliferation of chondrocytes in developing growth plates d/t pt mutation in FGFR3

33

What is the normal role of FGFR3?

Inhibition of normal proliferation of chondrocytes at the growth plate (this is constitutively active in achondroplasia)

34

True or false: achondroplasia is usually inherited

false--most are sporadic mutations

35

If achondroplasia is inherited, what inheritance pattern does it follow?

AD

36

True or false: homozygotes for FGFR3 mutation is lethal

True--Small chest wall = respiratory failure

37

What happens to the ones of proliferation in achondroplasia?

hypertrophied, narrowed, and disorganized

38

Which bones are usually short in achondroplasia?

All bones from formed cartilage

39

True or false: mental and reproductive development in achondroplasia is usually normal

True

40

What happens to the trunk with achondroplasia?

Normal length

41

What are the five zones of normal epiphyseal plate growth?

1. Reserve zone
2. proliferation
3. hypertrophy
4. Mineralization
5. Spongiosa

42

What happens to the zones of epiphyseal plates with achondroplasia?

Disorganization with transverse bars of bone sealing of plate growth

43

How is the head relative to the rest of the body with achondroplasia?

Enlarged with frontal bossing

44

What is the defect with osteogenesis imperfecta?

Abnormalities of type I collagen synthesis results in extreme bone fragility and thinning of bone cortex and trabeculae

45

What is the genetic cause of osteogenesis imperfecta, and what is the inheritance pattern?

Mutations in alpha 1 and 2 collagen chains

AD

46

What is type I OI?

increased risk of fracture, but is usually not deforming

47

What is type II OI?

Lethal--multiple fractures in utero with fetal demise

48

What is OI type III and IV?

Progressive deformities

49

What happens to the bone with OI?

Thinning of the cortex and trabeculae, with reduced numbers of trabeculae

50

What are the eye findings with OI?

Blue sclerae

51

What are the dental findings of patients with OI?

Amber, yellowish brown or translucent

52

What may happen to hearing with OI?

Decreased

53

True or false: patients with OI have a normal survival rate

True

54

What happens to the bones in type III and IV OI?

Bowing and breaking

55

What is osteopetrosis?

Marble bone disease--group of genetic diseases caused by decreased osteoclastic bone resorption, leading to diffuse skeletal sclerosis

56

What is the inheritance pattern of Osteopetrosis?

AR malignant
AD benign

57

What is the major cellular issue with osteopetrosis?

Defective osteoclastic activity, leading to abnormally thickened, heavily mineralized, and brittle bone

58

What causes the hematological abnormalities with osteopetrosis?

Encroachment on the bone marrow leads to reduced cellular proliferation

59

What are the features of the clinical presentation of osteopetrosis?

-Anemia/ thrombocytopenia
-Increased fractures
-CN palsies from compression
-Increased infx susceptibility

60

What is the role of bone marrow transplant with osteopetrosis?

helpful--provides progenitor cells which produce normal osteoclasts, which can reverse many of the skeletal abnormalities

61

What are the primary causes of osteoporosis?

Menopause
Age

62

What are the common secondary causes of osteoporosis?

Glucocorticoid induced
Immobilization induced

63

What, generally, is the pathophysiology of osteoporosis?

Reduction of bone mass

64

What are the histological findings of osteoporosis?

-Cortex and trabeculae are thinned, but remain of normal composition
-Increase porosity of the bone

65

By the time you're able to diagnose osteoporosis be x-ray, what percent of bone is lost?

40%

66

What bones are particularly affected with osteoporosis?

Trabecular bone, such as, weight bearing bones

67

what is the role of estrogen in preventing bone formation?

-Increased production of osteoprotegerin
-Increase in collagen synthesis by osteoblasts

68

What happens when estrogen levels fall with bone formation?

-Increased production of RANKL
-Decreased osteoprotegerin

69

What are wedge fractures?

When the anterior column of the vertebral body is compressed, leading to kyphosis, but usually with preservation of the spinal cord

70

What are burst fractures?

Axial load disrupts the anterior, middle, and/or posterior columns, frequently leading to disruption of the spinal cord

71

What happens to the vertebral bodies with osteoporosis?

Shorten

72

How do glucocorticoids cause osteoporosis? (3)

Increase in osteoclast survival, decrease in osteoblastogenesis, and increased apoptosis of osteocytes

73

What causes rickets and osteomalacia?

Defective mineralization caused by vit D deficiency

74

What is the effect of rickets in children?

heaping of unmineralized matrix leads to softening of bones and increased fractures

75

What are the causes of Vit D deficiency in the developed world?

malabsorption syndromes
Liver/kidney disease

76

What are the s/sx of osteomalacia?

-generalized pain
-fractures
-Mottled areas of bone lucency

77

What are the s/sx of rickets?

-bowing of the legs
-Frontal bossing
-Pectus carinatum

78

What is the Rachitic rosary? What causes it?

-The prominent knobs of bone at the costochondral joints of rickets patients
-Bones grow in thickness, but not length

79

What happens histologically with osteomalacia?

More osteoid, causing a more malleable bone